This invention relates to a carbon dioxide sensor, particularly a sensor for determining the partial pressure of carbon dioxide in a liquid, for example, blood. More particularly, the invention is concerned with a sensor which utilizes the phenomenon known as the "inner filter effect" to modulate the intensity of emission of a fluorescent compound and thereby provide a sensitive and accurate determination of the partial pressure of carbon dioxide in the medium under investigation.
The measurement in blood of pH levels and concentration of gases, particularly oxygen and carbon dioxide, is important during surgical procedures, post-operatively, and during hospitalization under intensive care and numerous devices for the measurement and display of said physiological parameters have been suggested in the art.
U.S. Pat. No. 4,003,707, Lubbers et al., and its reissue Pat. Re No. 31879, disclose a method and an arrangement for measuring the concentration of gases and the pH value of a sample, e.g. blood, involving the use of a fluorescent indicator enveloped by or sealingly embedded in a selectively permeable diffusion membrane. This patent discloses the use of beta-methyl-umbelliferone as a pH indicator.
The use of beta-methyl-umbelliferone as a fluorescent pH indicator was previously disclosed in an article by Raymond F. Chen, Analytical Letters 1[7], 423-428 [1968].
U.S. Pat. No. 4,200,110, Petersen et al discloses the use of a pH sensitive fluorescent indicator in conjunction with a fiber optic pH probe. The fluorescent indicator composition is enclosed within a selectively permeable membrane envelope.
In each of the above prior art references the determination of pH is dependent upon a change of intensity in the fluorescent emission of a suitable indicator. With suitable adjustment of the conditions under which the determination of pH is performed, a pH sensitive fluorescent indicator may be used to measure pCO.sub.2.
It has now been found that an improved sensor for determining the partial pressure of carbon dioxide may be based upon the fluorescence "inner filter effect". In such a sensor the emission of an inert fluorescent compound is modulated by the absorption of a pH indicator whose absorption spectrum overlaps the excitation and/or emission spectrum of the fluorescent compound.
The "inner filter effect" is a phenomenon which is known in the art and is described, for example, in "Fluorescence Assay in Biology and Medicine" by Sidney Udenfriend (1962) at pages 108-9. A brief summary of the state of the art relating to absorption-emission optrodes is to be found in an article "Optrodes: Chemically Selective Fiber-Optic Sensors" by S.M. Angel, at pages 38-47 in the April 1987 issue of "Spectroscopy.". This article describes the work of Hirschfeld and others who developed sensors based upon non-radiative energy transfer in which the emission spectrum of the fluorescer overlaps the absorption spectrum of the absorber and absorption occurs without true photon emission and absorption, but rather through a dipole-dipole energy transfer process. Such process is efficient only if the center-to-center molecular distance is less than 70.ANG. since the efficiency falls off as the inverse sixth power of the distance between molecules. In contrast thereto, the sensor of the present invention acts through radiative transfer, as hereinafter described. Notwithstanding the conventional view that radiative energy transfer is less efficient that non-radiative energy transfer, surprisingly it has been found that a viable sensor can be made by following the teachings of the present invention.
U.S. Pat. No. 4,495,293, Shaffar, discloses a fluorometric assay method involving the use of a fluorescer and a reagent system which changes the transmittive properties of the assay solution in the presence of the ligand under investigation and thereby modulates the intensity of fluorescent emission. The fluorescer-absorber system used in this method is an assay kit which reacts with and is used up by the sample solution.
The present invention provides a re-usable sensor for the selective determination of the partial pressure of carbon dioxide in a liquid.